GLP's ⏱ Half-life: ~11 hours FDA-Approved

Setmelanotide

Setmelanotide (Imcivree)

Updated March 30, 2026

Evidence at a Glance

Regulatory statusFDA-Approved
IMCIVREE, MC4R agonist; approved for POMC/PCSK1/LEPR & Bardet-Biedl obesity, plus acquired hypothalamic obesity (2026).
Human evidenceExtensive
Animal evidenceModerate

An MC4R agonist FDA-approved (IMCIVREE) for specific rare genetic and acquired forms of obesity, supported by controlled clinical trials.

What the research does not support

  • It is not approved or effective for common diet- or lifestyle-related obesity; it targets rare MC4R-pathway defects.
  • It is not a GLP-1 drug and does not work like semaglutide or tirzepatide.
  • It requires a qualifying genetic or clinical diagnosis and is not a general weight-loss peptide.
  • It does not cure the underlying genetic condition.
Half-Life
~11 hours
Purity
Pharmaceutical grade
Mol. Weight
1,117.3 Da
Form
Solution for subcutaneous injection (10 mg/mL multi-dose vial)

What is Setmelanotide?

Setmelanotide (Imcivree) is the first precision medicine for genetic obesity. Unlike general anti-obesity drugs, it targets a specific molecular pathway — the melanocortin pathway — and is only effective in patients with identified genetic mutations. It represents a paradigm shift toward genotype-guided obesity treatment.

Dosage Information (Research Use)

Adults: titrate from 1mg to 3mg SC once daily. Pediatrics ≥6 years: 1mg to 3mg based on weight. Prescription only for genetically confirmed obesity.

Reconstitution & Handling

Multi-dose vial — no reconstitution.

Half-Life & Pharmacokinetics

~11 hours

Reported Observations in Literature

Injection site reactions (45%), skin hyperpigmentation (34%), spontaneous penile erection in males (18%), GI disturbances. Pigmentation effect due to MC1R cross-activation.

Key Research References

  • Clément K et al. “MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency.” Nat Med. 2018;24:551-555

How Setmelanotide Works

Setmelanotide is a synthetic cyclic peptide that selectively activates the melanocortin-4 receptor (MC4R). In patients with genetic mutations upstream of MC4R (POMC deficiency, PCSK1 deficiency, or LEPR deficiency), the leptin-melanocortin satiety pathway is disrupted, causing severe hyperphagia. Setmelanotide bypasses these upstream defects by directly activating MC4R, restoring satiety signaling.

Research Applications

🔬 Genetic obesity syndromes (POMC, PCSK1, LEPR deficiency)
🔬 Bardet-Biedl syndrome obesity
🔬 Hypothalamic obesity

Research Findings

FDA-approved in 2020 for POMC, PCSK1, and LEPR deficiency obesity. Phase 3 trials showed 25.6% mean weight loss in POMC deficiency patients. Expanded to Bardet-Biedl syndrome in 2022. Hunger scores reduced by >30% in most treated patients.

Dosage & Administration

Adults: titrate from 1mg to 3mg SC once daily. Pediatrics ≥6 years: 1mg to 3mg based on weight. Prescription only for genetically confirmed obesity.

Safety & Side Effects

Injection site reactions (45%), skin hyperpigmentation (34%), spontaneous penile erection in males (18%), GI disturbances. Pigmentation effect due to MC1R cross-activation.

Important: All safety information is derived from published research, primarily animal studies. No controlled human clinical trial data exists unless explicitly noted. This compound is sold for research purposes only.

Quick Facts

Molecular Weight 1,117.3 Da
Half-Life ~11 hours
Purity Pharmaceutical grade
Form Solution for subcutaneous injection (10 mg/mL multi-dose vial)
Storage Refrigerate 2-8°C.

Key Research References

  • Clément K et al. "MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency." Nat Med. 2018;24:551-555

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